3- Chloropropionyl chloride

Rumpf et al. (97) studied the ultraviolet spectra of products obtained when 2-amino-4 phenylthiazole is acylated by /3-chloropropionyl chloride and y-chlorobutyrylchloride and showed that their structures were 94 and 95, respectively (Scheme 66). The open-chain intermediate to 95, 2-(3-... 

A 100 gallon lined jacketed kettle provided with cooling is charged with 100 lb of benzyl-amine and 150 liters of water. The mixture is cooled to 5°C and with stirring 119 lb of /3-chloropropionyl chloride and a solution of 45 lb of sodium hydroxide pellets in 40 liters of water are added simultaneously at such a rate that the temperature does not exceed 10°C. During this period the pH of the mixture should be on the alkaline side but below pH 9.5. When the addition is complete the pH should be about 8. The mixture is stirred overnight in the cold, and the solid product is filtered. The filter cake is reslurred with about BO gallons of water, filtered, and air-dried. Yield, 12B pounds. 

To this mixture, under continuous stirring and controlling of the reaction temperature to remain beyond 15°C, there is slowly added (3-chloropropionyl chloride. After addition of the acid chloride, stirring is continued for a further hour. Then with cooling there is added portionwise a small amount of water. Further amounts of water are introduced into the reaction mixture and the chloroform solution containing the /3-chloropropionyl a-ethylbenz-amidoxime is separated. 

MISCELLANEOUS FIVE-MEMBERED HETEROCYCLES Acylation with 3-chloropropionyl chloride of the... 

Esterification and amination 3-Chloropropionyl chloride, followed by amine (Scheme 10.57) Primary, secondary, tertiary and quaternary derivatives can be produced. Dyeable with reactive dyes, neutral to slightly acidic without salt... 

Additionally, the authors chose 3-chloropropionyl chloride as the immobilized building block in order to carry out a ring-expansion approach, which led to the generation of a 14-member library of thioxotetrahydropyrimidinones [85, 86], The initially prepared polymer-bound chloropropionyl ester was efficiently transformed into the corresponding diamines by transamination utilizing several primary amines. These diamine intermediates could also be obtained by treatment of the pure polymeric support with acryloyl chloride and subsequent addition of the appropriate amines (Scheme 7.74). 

All these reactions are promoted by Pd(II) species, and can be stoichiometric (Eq. 10) or catalytic (Eqs. 11-13, in the presence of Cu(II) salts or other oxidizing agents). 3-Chloropropionyl chloride from ethylene is conceivably formed through PdCl2 addition to the double bond followed by CO insertion and reductive elimination (Scheme 2). 

Attachment of the basic side chain to the phenothiazine nucleus by means of a carbonyl function apparently abolishes the usual CNS or antihistamine effects shown by most compounds in this class. The product azaclorzine instead is described as an anti anginal agent. Reduction of proline derivative 106 with lithium aluminum hydride gives the corresponding fused piperazine 107. Use of that base to alkylate the chloroamide 109, obtained from acylation of phenothiazine with 3-chloropropionyl chloride, leads to azaclorzine (110). ... 

Metal-Halogen Counpounds. One of the few examples of an olefin insertion into a metal-halogen compound has been reported by Tsuji. The reaction, which also supports the idea that sigma-bonded metal-carbon compounds are intermediates in the palladium chloride-olefin oxidation reaction, was the addition of carbon monoxide to the ethylene palladium chloride 7r-complex in nonaqueous solvents to produce a moderate yield of 3-chloropropionyl chloride (96). 

Acylation of A-hydroxy-2-phenylbutyramidine (112-1) with 3-chloropropionyl chloride in the absence of an added base proceeds as might be expected to give the product (112-2) from acylation on the more basic nitrogen. Heating this compound leads to the formation of the oxadiazole (112-3) almost certainly via the enol tautomer of the amide. Displacement of the terminal chlorine with diethylamine leads to the tertiary amine and thus proxazole (112-4) [123], a compound that is said to exhibit antispasmodic activity. 

Reactions of this type have been widely used for the synthesis of 1,5-benzoxazepines by the reactions of o-aminophenols and their derivatives with a variety of functionalized three-carbon chains. Thus reaction with 3-bromo-l-chloropropane gives (360) and reaction with 3-chloropropionyl chloride gives the analogous 4-oxo derivative. Similarly a,/3-unsatur-ated Icetones give (361), /3-ketoesters give (362), l,3-oxazolid-5-ones give (363), and the reaction of the sodium salt of N-methanesulfonyl-o-aminophenol with epichlorohydrin gives... 

This follows, since, if step C is slow, step B must also be slow and thus the addition intermediate would accumulate. Satchell found no spectrophoto-metric or kinetic evidence for this with either chloracetyl or /3-chloropropionyl chlorides. This conclusion is obviously of wide potential significance in the hydrolyses of acyl derivatives and even the observation of oxygen exchange during solvolysis (one of the main supports of the tetrahedral intermediate postulate) does not rule reaction (26) out, since the acylation could remain synchronous in part. 

Ethyl phenthiazine-2-carbamate 3-Chloropropionyl chloride Morpholine hydrochloride... 

To a solution of 10 g (0.035 mole) of ethyl phenthiazine-2-carbamate in 30 ml of anhydrous toluene is added dropwise 5.3 g (0.042 mole) of 3-chloropropionyl chloride, and the mixture is refluxed at 110-120°C for 4 hours, followed by clarifying the mixture with activated carbon and cooling it to room temperature. A precipitate of ethyl 10-(3-chloropropionyl)-phenthiazine-2-carbamate is removed by filtration. The yield is 10.2 g (77.5% of the theoretical amount), M.P. 169-170°C. 

Dimethyl-o-anisidine 3-Chloropropionyl chloride 3-Methyl piperidine Hydrogen chloride... 

Similar reactions occur in ethanol or acetic acid solution except that ethyl 3-ethoxybutyrate 2°) and 3-acetoxybutyric acid-acetic acid mixed anhydride 21>, respectively, are formed instead of 3-chloropropionyl chloride. 

Benzoxazepines are prepared similarly from o-aminophenols . 2-Aminophenol with 1,3-dibromopropane gives 1,4-benzoxazepine 395 and 3-chloropropionyl chloride gives the analogous 4-oxo derivative. Similarly, -unsaturated ketones give 396, -keto esters give 397, and l,3-oxazolidin-5-ones give 398. 

Addition reactions (1. 29). 1,5-Dichloropentanc-3-onc can be prepared by reaction of 3-chloropropionyl chloride with ethylene in methylene chloride in the presenee of anhydrous aluminum chloride. The yield of produci as a dark brown oil is 9.1 96%. 

The reaction flask is allowed to cool and is then immersed in an ice-watcr bath. A solution of 160-180 g. (4 4.5 moles) of sodium hydroxide pellets in 500 ml. of water is added slowly with stirring until the pH rises to 5. After the addition of400 ml. of ether, the products are transferred to a 5-1. separatory funnel and then shaken. I he darkly colored organic upper layer is separated and the aqueous layer extracted with two 500-ml. portions of ether. The combined ether extracts are dried over anhydrous magnesium sulfate and concentrated to about 800 ml. under reduced pressure in a rotary evaporator. The concentrated extract is transferred to a 1-1. round-bottomed flask and fractionated through a 25-cm. Vigreux column under reduced pressure. A forerun of dioxane is collected and then tctrahydro-4H-pyranc-4-onc distils as a colorless liquid, b.p. 59 60°/l3 mm. The yield is 102 112 g. (50 55%) for the two steps, based on 3-chloropropionyl chloride. 

The most recent source of these iminium ion precursors is the amide derived from 3-chloropropionyl chloride. Using the procedure reported by Ruhlmann for the preparation of 1-methoxy-l-trimethylsilyloxycyclopropane, Wasserman and Dion " converted the piperidide (58) to the 1-piperidino-l-trimethylsilyloxycyclopropane (59) by treatment with sodium metal in dry ether at 0°C. This reaction, which takes place smoothly and in high yield, serves as a short, inexpensive way to form the stable cyclopropanone equivalent. Further reaction of the silyl derivative (59) with tetrabutylam-monium fluoride in THF yields the corresponding carbinol amine (60). 

The formation of pyrroles by the reaction of the cyclopropylketimine (63) with HBF4 has been studied from a mechanistic point of view using 3-chloropropionyl chloride enriched with at the carbonyl carbon atom The C-NMR spectrum of the pyrrole formed from the cyclopropyl ketimine (63) shows enhancement of the peak at the 5-carbon in accord with mechanism A outlined in Scheme 27. Operation of process B analogous to the vinylcyclopropane rearrangement 63a would have led to enrichment at the 3-carbon of the pyrrole product. 

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